The overall goal of this project is to investigate the relationship between bisphenol A (BPA) levels and the risk of endometriosis in a population-based study of women in Washington State. BPA, a polymer used in polycarbonate plastic and epoxy resin, is present in a wide variety of consumer products, including beverage and food containers. BPA has been the focus of growing public concern and legislative action because migration of the chemical into food and beverages is the primary source of human exposure, which is believed to be chronic and widespread. While BPA has demonstrated strong estrogenic effects and is associated with developmental and reproductive effects in animal studies at levels lower than current human exposures, there is little information concerning the human health effects of BPA. This study will address that information gap, investigating the impact of adult BPA exposure on a prevalent and serious female reproductive-system disease. Endometriosis, the presence of endometrial tissue outside the uterus, affects approximately 8-10% of women of reproductive age in the U.S. and is associated with infertility and severe, chronic pelvic pain and dysmenorrhea. Endometriosis is an estrogen-dependent condition, and alteration in hormonal regulation has been proposed to contribute to disease onset and progression. The central hypothesis in this application is that exposure to BPA during the menstrual cycle results in structural changes in hormonally-responsive endometrial tissue that alter the dynamic regulation of tissue proliferation and breakdown and thus increase the risk of endometriosis. We further hypothesize that given the dynamic cyclic changes in endometrial tissue, the years from puberty to menopause are a critical period of susceptibility for exposure to BPA in relation to this disease. A population-based case-control study will be conducted among 18-49 year old female enrollees of a large mixed-model healthcare organization in western Washington State to address the primary Specific Aim: to determine if there is an association between urinary BPA levels and endometriosis risk. The secondary Aims are to test whether there is an association between BPA levels and endometriosis recurrence, and whether disease risk is affected by combined exposure to BPA and strong indicators of estrogenicity. To achieve these Aims, archived biosamples will be analyzed for total urinary BPA among 157 cases and 298 controls from the Women's Risk of Endometriosis study (V. Holt, PI), a five-year population-based case-control study of endometriosis that collected in-person interview, dietary intake assessment, anthropometric measurement, polymorphic gene (GSTM1, COMT) data and the two-year ancillary study (V. Holt, PI) that collected urine samples and determined lipid-adjusted serum levels of organochlorine compounds and polychlorinated biphenyls. All existing data will be linked with BPA data to address the Specific Aims. Results of this study address a serious gap in our knowledge of the safety of this chemical, and will inform regulatory efforts. PUBLIC HEALTH RELEVANCE: This is the first U.S. based study to investigate the relationship between adult exposure to the chemical bisphenol A (BPA) and endometriosis, a common female reproductive system disease that causes infertility and pelvic pain. BPA is the focus of current scientific and regulatory concern due both to widespread human exposure and to the association of BPA with developmental and reproductive system effects in animal studies. Because the proposed critical period for exposure to BPA in relation to this disease is during the reproductive years, the findings of this study have the potential for immediate public health impact.